title: Synthesis and structural characterization of the individual diastereoisomers of a cross-stapled alkene-bridged nisin DE-ring mimic.
abstract: Herein, we describe the synthesis, structural characterization, and synthetic use as an advanced intermediate of a cross-stapled alkene-bridged hexapeptide to mimic the DE-ring of the lantibiotic nisin. The linear precursor was cyclized by ring-closing metathesis to give the correctly folded bicyclic hexapeptide in a single step, and the four individual diastereoisomers were isolated, structurally assigned and characterized by HPLC, NMR and MS, respectively. The bicyclic hexapeptide was used as a versatile advanced synthon and was modified at its C- and N-terminus, among others, with an azide moiety to access a building block suitable for Cu(I)-catalyzed alkyne-azide cycloaddition-based ligation reactions.
authors.affiliation: Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands. D.T.S.Rijkers@uu.nl.
authors.forename: Jack C
authors.initials: JC
authors.lastname: Slootweg
authors.forename: Johan
authors.initials: J
authors.lastname: Kemmink
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
authors.forename: Dirk T S
authors.initials: DT
authors.lastname: Rijkers
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009561:Nisin / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D000900:Anti-Bacterial Agents; D009561:Nisin